Experience-dependent shaping of hippocampal CA1 intracellular activity in novel and familiar environments

Abstract

The hippocampus is critical for producing stable representations of familiar spaces. How these representations arise is poorly understood, largely because changes to hippocampal inputs have not been measured during spatial learning. Here, using intracellular recording, we monitored inputs and plasticity-inducing complex spikes (CSs) in CA1 neurons while mice explored novel and familiar virtual environments. Inputs driving place field spiking increased in amplitude-often suddenly-during novel environment exploration. However, these increases were not sustained in familiar environments. Rather, the spatial tuning of inputs became increasingly similar across repeated traversals of the environment with experience-both within fields and throughout the whole environment. In novel environments, CSs were not necessary for place field formation. Our findings support a model in which initial inhomogeneities in inputs are amplified to produce robust place field activity, then plasticity refines this representation into one with less strongly modulated, but more stable, inputs for long-term storage. We thank Min Ji Kim for technical assistance; Joshua Dudman, Adam Hantman, Michael Tadross, Nelson Spruston, Jeffrey Magee, Aaron Milstein, Simon Peron, and members of the Lee Lab for helpful discussions and comments on the manuscript; Steve Bassin and Jason Osborne for mechanical engineering and machining; Vivek Jayaraman, Hannah Haberkern, Christopher Bruns, and Sean Murphy for contributions to the development of the virtual reality software; and Magnus Karlsson and Lakshmi Ramasamy for electrical engineering. This work was supported by the Howard Hughes Medical Institute.